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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Influence of serum and albumin on echinocandin pharmacodynamics

Nasar, Aasya Saira 08 November 2012 (has links)
Background: The use of human serum (HS) or bovine serum albumin (BSA) during susceptibility testing may help discriminate between echinocandin susceptible and resistant C. albicans and C. glabrata strains. However, the influence of these protein components and that of specific FKS mutations on the in vitro potency of the echinocandins remains unclear. Our objective was to evaluate the in vitro pharmacodynamics of the echinocandins in the presence and absence of these biological matrices against resistant C. albicans and C. glabrata isolates. Methods: Thirteen C. albicans clinical isolates (2 wild-type and 11 FKS mutants (F641S and S645P) and twenty C. glabrata clinical isolates (16 FKS mutants and 4 with unknown resistance mechanisms) were used. MICs were measured in duplicate according to the CLSI M27-A3 guideline for caspofungin, micafungin, and anidulafungin in RPMI, or RPMI supplemented with either 5% HS or 5% BSA. Pharmacodynamic analysis was also performed with the XTT viability assay, and non-linear regression analysis was usedto determine the IC50 values. Differences in geometric mean (GM) MICs and mean IC50 values were assessed by ANOVA and the Student’s t-test. Results: The addition of BSA significantly increased the GM MIC (6-24 fold) and IC50 (9-25 fold) of each echinocandin compared to RPMI (p < 0.0001) for isolates with FKS mutations. Increases in MIC (4-12 fold) and IC50 values (3-5 fold) were also observed with the addition of HS. Although increases in MICs and IC50s were also observed against the wild-type isolates, these values remained < 1 μg/mL for each echinocandin. When comparing the results of specific FKS mutations in C. albicans, the MIC and IC50 values were higher in each growth condition for isolates with S645P mutations (HS & BSA GM 8.0 & 12 μg/mL; mean IC50 5.5 & 21 μg/mL, respectively) compared to those with F641S mutations (HS & BSA GM 3.7 & 9.8 μg/mL; IC50 4.0 & 16 μg/mL, respectively). Conclusions: The addition of HS and BSA significantly influenced the pharmacodynamics of the echinocandins, but to different degrees. The specific FKS mutation may influence these in vitro potency changes, but further work is needed to evaluate these matrices and standardize echinocandin testing in their presence. / text
2

Die Erfassung des Flow-Erlebens

Rheinberg, Falko, Vollmeyer, Regina, Engeser, Stefan January 2003 (has links)
Ausgehend von einer Charakterisierung des Flow-Erlebens als gaenzliches Aufgehen in einem glatt laufenden Taetigkeitsvollzug, den man trotz hoher Beanspruchung noch unter Kontrolle hat, wird auf die Erfassung dieser Motivationskomponente eingegangen. Dargestellt und diskutiert werden Vor- und Nachteile der bisherigen qualitativen (Interviews) und quantitativen Flow-Erfassung (Experience Sampling Method (ESM)) . Ausfuehrlicher wird eine "Flow-Kurzskala" (FKS) beschrieben, die mit zehn Items alle qualitativ verschiedenen Komponenten des Flow-Erlebens oekonomisch und reliabel erfasst. Sie liefert einen Gesamtwert sowie Werte fuer zwei Subskalen (glatter automatisierter Verlauf sowie Absorbiertheit). Daneben erfassen drei zusaetzliche Items die Besorgnis in der aktuellen Situation. Berichtet werden Vergleichskennwerte aus punktuellen Messungen und ESM-Studien. Die hoechsten Werte fuer Flow und Besorgnis wurden bislang bei Graffiti-Sprayern gefunden. Bei einer intellektuell herausfordernden Aufgabe (Postkorbuebung) sind die FKS-Werte mit der Hoffnung-auf-Erfolg-Komponente des Leistungsmotivs korreliert. Furcht-vor-Misserfolg korreliert dagegen mit dem Besorgniswert der FKS. Flow waehrend der Bearbeitung von Uebungsaufgaben fuer Statistik lieferte einen signifikanten Beitrag zur Vorhersage der nachfolgenden Klausurleistung. Dieser Beitrag blieb erhalten, auch wenn Faehigkeitsmasse kontrolliert wurden. (Buch/A.G. - ZPID)

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